Prostate cancer diagnosis: twice as accurate?
About mice and humans: prostate carcinoma
Vladimir Fradkin, Deutsche Welle
Today, the early diagnosis of prostate cancer is based on a test that in two cases out of five gives a false alarm. Now scientists have proposed a new test that allows, according to preliminary data, to double the reliability of diagnostics.
The earlier the disease is detected, the easier it is to treat it and the higher the probability of cure. This simple consideration, valid for any disease, is especially clearly manifested in the case of cancer, first of all – some of its most aggressive and rapidly progressing forms. A clear example of such an oncological disease, where early diagnosis is a matter of life and death, can be prostate carcinoma or prostate cancer.
Since older men very often have an adenoma, or benign hyperplasia, that is, an overgrowth of the prostate gland, which may eventually degenerate into carcinoma, doctors recommend that such patients undergo a special test every year.
Instead of one protein, many thousandsWe are talking about a blood test, during which doctors determine the presence and concentration of a special protein marker PSA, that is, a prostate-specific antigen.
The trouble is that this test is not reliable enough: for one reason or another, the PSA level may be noticeably increased in perfectly healthy men. Now Swiss scientists have proposed a new approach to the development of cancer tests and tested it on the example of prostate carcinoma. Instead of examining a blood sample for the presence of a single protein, they analyze it for the presence of many thousands of proteins at once.
It is quite obvious that such an analysis can provide much more valuable information. However, this approach is also associated with certain difficulties," says Professor Wilhelm Krek, a researcher at the Institute of Cell Biology at the Higher Technical School in Zurich: "It turned out that the protein profile of the patient obtained in this way also does not necessarily indicate cancer, but may be associated, for example, with nutritional characteristics this particular person. That is, a completely new technique is needed here, which makes it possible to detect the occurrence of cancer with high reliability."
Instead of many thousands of proteins – 126If with a traditional blood test for one marker, doctors receive too little information for a reliable diagnosis, then with an analysis for thousands of proteins, there is too much information.
This abundance of data makes it almost impossible to compare the biochemical profiles of healthy and sick people. Therefore, Swiss scientists recommend focusing primarily on known cancer genes. One of them is Pten. The protein product of this gene is a phosphatase, an enzyme involved in the regulation of the cell cycle and performing the function of a tumor suppressor. Mutations of this gene lead to the development of various kinds of malignant neoplasms, including prostate carcinoma.
During the experiments, Zurich scientists artificially reproduced the corresponding defect of this gene in male laboratory mice, which led not only to the development of prostate cancer in animals and an increase in PSA, but also to very significant changes in the entire protein profile. Professor Krek says: "Then we compared a set of proteins in the blood of healthy mice with a set of proteins in the blood of mice with cancer, and thus revealed a protein profile characteristic of the mutation of the Pten gene, and hence for prostate carcinoma."
Specifically, the Zurich researchers were able to identify very significant differences in 126 proteins. Since laboratory mice, unlike humans, are kept in standard vivarium conditions, the differences found are most likely really related to prostate cancer, and not to nutritional characteristics and other extraneous factors.
Instead of 126 proteins – two testsAnyway, Professor Krek decided to test the information obtained on mice in humans.
In this undertaking, the database of the cantonal hospital in St. Gallen turned out to be extremely useful, in which blood and tissue samples from men suffering from various prostate diseases have been collected and stored for many years. In this data set, the scientist tried to discover characteristic patterns associated with changes in 126 proteins identified in experiments on mice. "From these candidates, we were able – in close cooperation with computer scientists who developed the appropriate models – to identify 4 proteins that allow for reliable diagnostics," says Professor Krek.
However, the scientist exaggerates somewhat about reliability: the new test also does not always distinguish malignant prostate changes from benign ones. That is, it cannot replace the PSA test. However, the combination of the two tests really significantly increases the reliability of the diagnosis. If two out of five positive PSA test results are false on average, then the use of two tests reduces the percentage of errors by half: only one out of five positive results turns out to be false. However, all these calculations are based not yet on real clinical statistics, but on the analysis of the archival database of the cantonal hospital.
And final conclusions can be made only after the completion of large-scale clinical trials with the participation of a large group of elderly male volunteers. Such tests are expected to begin in the near future. "Of course, this work will take more than one year," says Professor Krek, "but I think that the profile of four proteins we have identified is a significant step forward towards an accurate and reliable diagnosis of prostate carcinoma."
Portal "Eternal youth" http://vechnayamolodost.ru29.03.2011